Primary objective：

1. To evaluate the effect of Itraconazole ( CYP3A and P-gp inhibitors) on HMPL-453 pharmacokinetics(PK) in healthy subjects
2. To evaluate the effect of Rifampin (CYP enzyme inducer) on HMPL-453 pharmacokinetics (PK) in healthy subjects

Secondary objectives：

To evaluate the safety of HMPL-453 with and without itraconazole or rifampin following a low-fat meal in healthy subjects

Exploratory objectives:

1. Assess cholesterol and 4β- hydroxycholesterol in plasma CYP3A4 Biomarker Concentration Levels ;
2. Explore proarrhythmic effect of HMPL-453 [Results of exploratory objectives analyses will be reported separately and not included in the clinical trial Study Report (CSR)]

Inclusion Criteria:

1. Has fully understood and voluntarily signed the ICF for this study.
2. Male or female 18 years of age or older.
3. Body mass index (BMI) at screening: 18 < BMI ≤ 29.9 kg/m 2 and weight ≥ 50 kg for men and ≥ 45 kg for women.
4. Female subjects of childbearing potential use highly effective contraception from 1 month prior to signing ICF through 6 months following the last HMPL-453 dose and agree not to donate ova for reproductive purposes during this period (or oocytes). Acceptable forms of highly effective contraception include total abstinence, bilateral tubal ligation, oral or injectable contraceptives, intrauterine devices, or vasectomy in the partner. All hormonal contraception must be combined with barrier measures such as condom use by the spouse.
5. Male subjects agree to use highly effective contraception from first dose until 3 months after the last HMPL-453 dose. Subjects should refrain from donating or freezing sperm during this period .
6. Subject is willing and able to comply with the protocol in all aspects.

Exclusion Criteria:

1. Patients with previous or excluded diseases with abnormal clinical manifestations during the screening period, including but not limited to neurological/psychiatric system, respiratory system, cardiovascular and cerebrovascular system, gastrointestinal system (any history of gastrointestinal diseases affecting oral or absorption of drugs), blood and lymphatic system, liver and kidney function, endocrine system, and immune system diseases.

2. Subjects with clinically significant (eg, requiring medical intervention or surgical treatment) disease within 8 weeks or clinically significant (requiring systemic anti-infective treatment, such as oral or intravenous antiviral, antibacterial, antifungal therapy, etc) infection within 4 weeks prior to the first dose.

3. Subject has a current or past history of retinal detachment.

4. Use of any medications (including prescription drugs, over-the-counter drugs, herbal preparations and formulas, etc.) and health products within 2 weeks prior to the first dose.

5. Hypericum perforatum requiring 4 weeks or 5 half-lives (whichever is longer) prior to first dose 3 weeks) Use of any drugs that inhibit or induce cytochrome P450 enzymes or P- glycoprotein inhibitors (See Appendix 12.3 for details).

6. Subject has received blood or blood products 4 weeks prior to first dose and donated blood or blood products 8 weeks prior to first dose.

7. Subjects who cannot guarantee not to take any food, juice or beverage containing alcohol, grapefruit, Seville oranges and caffeine within 72 hours prior to the first dose until the end of the trial; and have special requirements for diet and cannot comply with the unified diet.

8. Smoking more than 10 cigarettes per day within 3 months prior to screening and unable to completely abstain from smoking during the study.

9. Regular drinkers 6 months prior to screening, defined as drinking more than 14 units of alcohol per week ( 1 units = 360 mL Beer or 45 mL spirits or 150 mL wine containing 40% alcohol; positive alcohol screen.

10. Participated in other clinical trials of drugs or medical devices 3 months before taking study drug, or failed online screening.

11. Fainting, halo, or difficulty collecting venous blood.

12. Subject is hypersensitive to any of the study medications (or their excipients) administered in this study.

13. Female subject is pregnant or lactating, or has a positive pregnancy test result.

14. The subject had clinically significant abnormalities in physical examination, abdominal B scan (hepatobiliary pancreatic splenorenal), and laboratory test results at Screening.

15. Abnormal vital signs (excluded if any of the following: systolic blood pressure:

    < 90 mmHg or > 140 mmHg , diastolic blood pressure: < 60 mmHg or > 90 mmHg ; pulse: < 60 beats

    /min or > 100 beats/min; Body temperature < 35.8 ° C or > 37.3 ° C (frontal temperature).

16. Subjects with keratopathy confirmed by ophthalmic examination, including but not limited to bullous keratopathy, band keratopathy, corneal abrasion, corneal ulcer, keratitis, or other ophthalmic abnormalities considered by the investigator as inappropriate for participation in this study.

17. The subject had clinically significant ECG abnormalities, including a prolonged baseline QTcF (eg, QTcF interval > 450 ms in males and QTcF interval > 460 ms in females), or a family history of QTc prolongation syndrome or sudden death. If ECG does not show QTcF results, use the following formula for calculation: QTcF = QT/RR .

18. Presence of drug abuse (including morphine, methylenedioxyamphetamine, methylamphetamine, tetrahydrocannabinolic acid, ketamine, cocaine urine drug abuse screen positive) at Screening.

19. Human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), hepatitis C virus Positive (HCV) antibody or syphilis-specific antibody.

20. Abnormal chest X-ray (anteroposterior) findings with clinical significance (such as active infection, high-risk nodules, etc.).

21. Any other condition that, in the judgment of the investigator, would make the subject inappropriate for entry into this study.